EpCAM Aptamer siRNA chimeras: Therapeutic efficacy in epithelial cancer cells

Abstract

In the era of personalized medicine as well as precision medicine, targeted therapy has become an integral part of cancer treatment in conjunction with conventional chemo-and radiotherapy. We designed aptamer-siRNA chimeras that can specifically target cancers expressing EpCAM, a stem cell marker and deliver the specific siRNA required for therapy response. The siRNAs were chosen against PLK1, BCL2 and STAT3 as these oncogenes play prominent role in tumour progression of several cancers. Targeted delivery of EpCAM-siRNA chimeras resulted in cell death in several cancer cell lines such as cancers of the breast, lung, head and neck, liver and retinoblastoma. In vivo analysis of EpCAM-siRNA chimera mediated silencing on RB xenografts tumour model showed increased tumor reduction in all the three EpCAM-siRNA treated conditions. However, regulation of PLK1 exhibited higher efficacy in tumour reduction. Therefore. We studied signaling mechanism using global phosphoproteomics analysis. An increased P53 mediated downstream signalling pathway might have enabled increased apoptosis in the cancer cells. In conclusion, this study demonstrated the efficacy of EpCAM aptamer chimeras coupled to siRNA gene silencing for targeted anti-cancer therapy.

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

“…In the case, PLK1, BCL2, and STAT3, three important proteins with high relevance in tumor growth, were selected. They tested various chimeras with positive results in cancer cell lines of breast, lung, head, neck, liver, and retinoblastoma [67].…”